Endocrine glands secrete hormones that mediate slower, but longerlasting. Endocrine system functions more as a regulatory than a command system

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1 The Endcrine System 1 Tpics Types f cell signalling Fur types f cell signalling (majr) Fur types f hrmnes (majr) Types f hrmnes Hrmne receptrs Majr endcrine glands Majr hrmnes The hypthalamus and pituitary The thyrid gland The adrenal gland The pancreas / insulin and diabetes The pineal gland Atrial natriuretic peptide 2 Adrenal Gland Nervus System: Neural netwrks / rapid signalling Endcrine System Endcrine glands secrete hrmnes that mediate slwer, but lngerlasting respnses Endcrine system functins mre as a regulatry than a cmmand system Secretes hrmnes that mve thrugh bld r extracellular fluid Respnse can be very rapid (e.g. adrenalin)

2 Adrenal gland has tw parts: Or very slw (e.g. changes in prtein synthesis r gene transcriptin) Outer crtex Prduces sterid hrmnes Inner medulla Releases adrenaline Part f fight r flight respnse The mre crtisl yu have, the mre rapidly yu age 3 Circulating Hrmnes Classic endcrine hrmnal respnse Endcrine gland that cntains cells which synthesize and secrete hrmnes Hrmnes diffuse thrugh extracellular fluid and they circulate in the bld Mve thrugh bld t these target cells and activates their receptrs 4 Neurcrine Endcrine Signaling Hrmnes can als riginate / mve frm nerves Referred t as neurhrmnes Rather the cell f a gland prducing and secreting hrmnes they have a nerve ding this functin Frm the nerve it is transprted thrugh extracellular fluid and bld Hrmnes acts n target tissues Hypthalamus has neurns which prduces tw hrmnes: ADH Oxytcin

3 The axns frm these cells are fund n the nerve terminals (psterir pituitary) 5 Paracrine and Autcrine Signaling Paracrine endcrine signalling An endcrine releases hrmnes Hrmnes dn t travel thrugh the bld Instead they mves thrugh ne cell type t anther cell type in the extracellular fluid (shrt distances) Autcrine endcrine signalling Cell releases hrmnes Hrmnes feeds back and has an effect n the same cell that released it This can ccur in nerves -e.g. acetylchline (paracrine manner) Released and travels t target cell via extracellular fluid e.g. dpamine (autcrine manner) Released and travels t target receptr n the same cell Yu can ften have an autcrine effect n the cell which either inhibits r accelerates the release f the paracrine substance i.e. release hrmnes that: Inhibits release f paracrine substance Accelerates release f paracrine substance 6 Cell Signalling Regulatins Fur majr methds f signalling Classical endcrine signalling Release f hrmne (frm endcrine cell) transprted in bld binds t receptr prtein respnse Neurendcrine (Neurcrine) signalling

4 Release f hrmne frm nerve bld receptr respnse Paracrine regulatin Release f hrmne diffusin thrugh extracellular fluid receptr respnse Autcrine regulatin Release f hrmne diffusin thrugh extracellular fluid receptr n the same cell respnse 7 Types f Hrmnes: Amines Fur majr types f hrmnes Fatty Acids Sterids Peptides Amines Tyrsine-based Hydrphilic -i.e. water lving Three hrmnes are referred t as catechlines (cntains catechl grup and amine grup) Dpamine Neurtransmitter Epinephrine Hrmne Nrepinephrine Either a neurtransmitter r a hrmne Adrenal glands are wrapped arund the upper prtins f the kidney Adrenaline = Epinephrine

5 Epi = arund Nephrs = kidney Nradrenaline = nrepinephrine Bth dpamine and nrepinephrine functins as neurtransmitters Epinephrine des nt Nrepinephrine and epinephrine functin as hrmnes Dpamine des nt 8 Peptides Peptide hrmnes The liver is always prducing angitensingen (a prtein) Angitensingen angitensin (a peptide) In respnse t sme stimuli (e.g. lw bld pressure), kidney prduces rennin (enzyme) and releases it int the bld Rennin then acts n angitensingen and prduces angitensin I Angitensin I circulates thrugh the lung capillaries and kidneys and is expsed t ACE (enzyme; angitensin cnverting enzyme sufficient t knw it just as ACE) ACE cnverts angitensin I t angitensin II Angitensin II effects bld pressure regulatin and smtic and in regulatin Angitensin II triggers the adrenal crtex t release aldsterne 9 Sterids / Fatty Acids All sterids are derivatives f chlesterl Prgesterne Teststerne Estradil

6 Aldsterne Crtisl Hydrphbic Bind receptrs within the cell Transprted in the bld via carrier prteins Fatty Acids Insects use fatty acids as hrmnes Frm a mammalian pint f view there are three main hrmnes: Amines Peptides Sterids 10 Hrmne Receptrs: Cell Surface Receptrs Hrmnes exert effects either by acting n cell surface receptrs hrmne cming frm the bld diffusing thrugh the extracellular fluid t bind t a receptr the binding will set in mtin a series f reactins finally we end up with ne r mre receptr mlecules that bring abut the respnse within a cell diffusing int the cell and interacting with receptrs in the cytsl r nucleus hrmne is released thrugh secretry cell intr the extracellular fluid and bld hrmne circulates thrugh the bld and then binds t a receptr cell binding hrmne t receptr causes several pathways: the prductin f an effectr mlecule in cytplasm

7 the prductin f an effectr mlecule that mves int nucleus and alters transcriptin Cmmn effectr mlecules in the cytplasm: Kinase (adds phsphates) Phsphatase (remves phsphates) Brings abut a respnse within prteins and enzymes Enzymes that are either activated r deactivated ccur thrugh phsphrylatin / dephsphrylatin A large majrity f secndary messengers that leads t effectr mlecules is thrugh phsphrylatin / dephsphrylatin 11 Intracellular Receptrs We can als have hrmne receptrs inside cells In the cytplasm Diffuses acrss the plasma membrane instead f binding t a surface receptr Binds t a receptr in the cytsl receptin Receptr hrmne cmplex mves int nucleus and triggers a respnse transductin Affects gene transcriptin respnse In the nucleus Diffuses acrss membrane int cytsl int nucleus binds in nucleus Receptr hrmne cmplex binds with dna t alter gene transcriptin 12 Aldsterne

8 Example f intracellular receptr: Aldsterne Released by uter regins f adrenal glands Occurs when [Na+] falls in bdy fluids Angitensin II causes this release High plasma [K+] Outer regins f adrenal glands release Aldsterne 13 Functin f Aldsterne Aldsterne mves int the cell and binds t a receptr Receptr-hrmne cmplex mves within the nucleus and alters gene transcriptin Increases in transcriptin will lead t increase in prtein synthesis Increase in prductin f sdium channels Sdium channel can get inserted in the plasma membrane Aldsterne ccurs in kidney tubule cells (pre-urine) In respnse t angitensin II and high plasma/lw sdium the adrenal crtex releases Aldsterne Aldsterne mves int the cell and interacts with the receptr Effect f Aldsterne synthesizes Na/K Channels and Na-K ATPases Stimulates existing Na and K channels t pen as well Sdium mves frm the pre-urine acrss the tubular epithelial cell Sdium is then pumped int the extracellular fluid int the bld Aldsterne has served t pull sdium back ut f the urine and bring it back int the bld Na re-absrptin in the kidney Aldsterne des the ppsite fr ptassium

9 Ptassium is mved frm the bld thrugh the extracellular fluid int the urine K secretin in urine 14 Majr Endcrine Glands and Hrmnes Hypthalamus (Brain) Prduces and secretes releasing and inhibiting hrmnes that regulate secretins by the anterir pituitary Anterir pituitary secretes ACTH / TSH / FSH / LH These stimulate ther glands as well as prlactin / GH / MSH / endrphins Prduces ADH and xytcin Stred and released in the psterir pituitary Adrenal crtex Secretes crtisl and Aldsterne Adrenal medulla Secretes epinephrine and nrepinephrine Pineal gland Secretes melatnin Aids in sleep Thyrid gland Secrets thyrxine and triidthryrnine and calcitnin Aids in metablism Parathyrid glands Secrete parathyrid hrmne Pancreas Islets f Langerhans secrete insulin and glucagn

10 Bld glucse regulatin Ovaries Secrete estrgens and prgestins Testes Secrete andrgens 15 The Hypthalamus and the Psterir Pituitary ADH and xytcin are prduced in the cell bdy f the hypthalamus and secrete thrugh the nerve terminals f the psterir pituitary ADH antidiuretic hrmne anti water flw Oxytcin has effects n the uterus and mammary glands Stimulates cntractins and milk prductin ADH causes kidney t reclaim water r prduce less urine Prevents the kidney frm prducing large vlume f urine Receptrs fr ADH are inhibited by alchl Large dilute amunts f urine are prduced Alchl is a diuretic 16 The Hypthalamus and the Anterir Pituitary Hypthalamus prduce and release RH (stimulating hrmnes) and IH (inhibiting hrmnes) Released thrugh nerve terminals f hypthalamus Released int a capillary bed Mve thrugh a prtal vein t a capillary bed in anterir pituitary In anterir pituitary, RH and IH trigger endcrine cells t release a number f substances Anterir pituitary hrmnes signals rgans t release mre hrmnes Hypthalamus is als the bdy s center f temperature regulatin

11 17 Anterir Pituitary Hrmnes Imprtant AP (anterir pituitary) hrmnes: TSH thyrid-stimulating hrmne Stimulates thyrid gland ACTH adrencrtictrpic hrmne Stimulates adrenal crtex GH grwth hrmne wrks with thyrid hrmnes t increase metablism and prmte grwth FSH / LH gnadtrpins Affect reprductive rgans Hrmnes released frm ne gland that acts n anther gland are called trpic hrmnes 18 Anterir Pituitary Hrmnes Trpic effects nly: FSH fllicle-stimulating hrmne / LH luteinizing hrmne Target: testes r varies TSH Target: thyrid ACTH Target: adrenal crtex Nn-trpic effects (nt required t knw in detail) Prlactin MSH Nn-trpic and trpic effects: GH

12 19 Hypthalamic-Pituitary-Thyrid Axis HPT axis is an example f thyrid and pituitary hrmnes wrking ne after anther t lead t an effect that releases hrmnes Hypthalamus releases thyrid-releasing hrmnes Mves thrugh prtal vein t anterir pituitary Causes AP t prduce thyrid-stimulating hrmnes TSH mves thrugh bld t thyrid gland t release thyrid hrmnes Thyrid hrmnes increase metablism prmting grwth regulating develpment in maturatin Thyrid hrmnes: T4 thyrxine T3 triidthryrnine Thyrid hrmnes can release hrmnes that are independent f this axis these independent hrmnes are invlved in bld calcium regulatin 20 Thyrid and Parathyrid Glands: Calcium Regulatin Thyrid glands release calcitnin when calcium plasma levels are ging up Decreases calcium level If calcium plasma levels g dwn, parathyrid hrmnes are released Increases calcium level 21 Calcium Hmestasis If plasma calcium ges up, thyrid glands release calcitnin t make it g dwn If calcium levels g dwn, parathyrid gland releases hrmnes (PTH) t make it g up Three target rgans that affect calcium levels in the bld: Kidney

13 Increases r decreases its rate f secretin r uptake f calcium If calcium levels are high, kidney excretes calcium If t lw, kidney increases its uptake f calcium Invlved in the activatin f a frm f vitamin D called calcitrl This substance helps t reabsrb calcium during lw calcium levels Bne Calcium levels lw PTH triggers bne t give up its calcium t the bld If levels are t high, calcitnin triggers the bnd t take up calcium frm the bld Intestine Calcium levels lw increase rate f absrptin f calcium frm ingested fd 22 Hypthalamus-Pituitary-Adrenal Axis Inner crtex prduces sterids Outer medulla prduces catechlines Example f an initial stimulus lw bld glucse Triggers hypthalamus t release crticl trpic releasing hrmnes Triggers anterir pituitary t release ACTH releasing hrmnes Triggers adrenal crtex t release crtisl Crtisl causes bld glucse t increase (main idea t be grasped) Crtisl has negative feedback Inhibits hypthalamus frm release f crticl trpic releasing hrmnes Inhibits anterir pituitary frm release f ACTH 23 The Adrenal Gland

14 A general stress respnse Medulla is signalled t release mre adrenaline by sympathetic nerve stimulatin General fight r flight respnse invlving adrenal glands We ptimize cardivascular respiratry functin, increase bld pressure, increase breathing and metablic rate and prvide mre fuel in the shrt term 24 Adrenergic Receptrs (Adrenceptrs) Catechlines wrk by binding t particular receptr type called adrenal receptrs Tw main types f receptrs: Alpha Beta Can cnvert ATP AMP Bth have different secndary messenger systems Leads t hrmnes having different respnses n the same type f tissue depending n the present receptr Epinephrine acting n alpha receptr vessel cnstrictin (intestinal) Epinephrine acting n beta receptr vessel dilatin (skeletal) 25 The Adrenal Gland in Bny Fish Mammals have a medulla with distinct medulla and distinct crtex Fish dn t have adrenal glands The cells that prduce catechlines and sterids are fund lying in a large vein the psterir cardinal vein (equivalent t the vena cava in humans) which flws int the heart There is sympathetic nerve stimulatin The adrenal medulla is innervated by sympathetic nerves which stimulates the release f catechlines but there are ther prcesses that prduce this release as well (situatinal)

15 26 The Pancreas and the Islets f Langerhans Pancreas has bth endcrine and excrine functin Excrine functin pancreas secreting digestive enzymes int the intestines Endcrine functin pancreas takes up digestive enzymes frm the intestines Thrughut the pancreas, there are grupings f cells called islets f langerhans (cntaining beta and alpha cells) Beta cell insulin (lwers bld glucse) Alpha cell glucagn (raises bld glucse) Beta and alpha cells regulate bld glucse levels 27 Insulin As plasma glucse ges up, plasma insulin als ges up Insulin helps t mve glucse int cells -i.e. lwer bld-glucse levels Insulin activates glucse transprters, allwing cells t take up glucse Fd in gut triggers synthesis f insulin in anticipatin f increasing bld-glucse levels 28 Bld Glucse Regulatin Beta example: Initial stimulus: high bld glucse levels Beta cells in pancreas release insulin Insulin triggers cells in liver and ther rgans t take up glucse In the liver glucse becmes glycgen (fr strage) Bld glucse levels decrease Alpha example: Initial stimulus: lw bld glucse levels

16 Alpha cells in pancreas release glucagn Glucagn signals liver t start breaking dwn glycgen t release glucse int the bld Bld glucse levels increase 29 Diabetes Mellitus Type I (insulin dependent) Failure f beta cells t release insulin int the bld Autimmune disease Can be treated with insulin injectins Very small fractin f ttal diabetes cases (~10%) Type II (nn-insulin dependent) Resistant t insulin Beta cells can prduce and release insulin int the bld but cells aren t respnding t insulin Insulin is unable t activate the messenger systems n the cell that allw fr glucse intake Assciated with lng-term besity Huge fractin f ttal diabetes cases (~90%) 30 Acute Cmplicatins f Diabetes Mellitus Diabetic Ketacidsis Cells aren t getting enugh glucse because they are nt taking up insulin Start t use fatty acids as energy surce Liver cnverts fatty acids int ketnes Ketnes then circulate in the bld which prduces symptms similar t alchl intxicatin Dehydratin Diabetes can cause dehydratin

17 High levels f glucse in the bld ends up being in urine (smtic reactive mlecule) If glucse is in the urine, yu have t flush it ut with mre water The mre glucse t get rid f the mre water yu have t get rid f dehydratin 31 Lng-Term Cmplicatins f Diabetes Mellitus Athersclersis Build up fatty acid depsits in the inside f bld vessels Accumulatin f fatty acid depsits leads vessel t becme narrwer and narrwer Narrw vessel inhibits bld flw Reduced r inhibited bld flw leads t heart tissue death heart attack / strke Nitric xide in healthy peple keeps bld vessels dilated (less narrw) Diabetes dn t respnd t nitric xide s it desn t dilate their bld vessels when it becmes clgged Reduced peripheral circulatin Reduced bld flw leads t damage in peripheral circulatin gangrene 32 Acute Cmplicatins f Diabetes Mellitus Blindness (Diabetic Retinpathy) Acute (shrt term) cmplicatin f diabetes Bld vessel damage in the eye reduced bld and xygen supply (ischemia) cmpensates by frming new bld vessels (nevascularisatin) new vessels are very weak (thin walls), break easily and haemrrhage damaged eye tissue abnrmalities in visin 33 The Pineal Gland Secretes melatnin (helps humans sleep)

18 Release f melatnin triggered by darkness (prduced mre in the dark than in the light) 34 Atrial Natriuretic Peptide (ANP) Feedback system Secreted by cells in the atria (heart) in respnse t a stretch in the atrial wall (due t increase in plasma vlume) Bld vlume increase bld pressure increase atrial stretch atrial release f ANP ANP directly inhibits Na+ reabsrptin and inhibits Aldsterne secretin which als inhibits Na+ reabsrptin bld vlume decreases bld pressure decreases

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